Tomasz Heyduk Lab

Research areas

Our lab has two major research interests:

1. Mechanisms of transcription initiation and its regulation.

Our main interest is to understand the mechanism of transcription initiation by bacterial RNA polymerase (RNAP). RNAP interacts with conserved -10 and -35 promoter elements to recognize the promoter and to form an open complex in which the DNA duplex around transcription start site melts. The focus of our current research is to obtain molecular understanding of promoter melting step of the initiation reaction with a particular emphasis on the role of the spacer DNA (a non-conserved DNA sequence connecting -10 and -35 promoter elements). Our recent results indicate that spacer DNA plays an important active role in integrating the functional consequences of RNAP contacts with -10 and -35 promoter element. Our additional interest is in determining the mechanism of promoter escape by RNAP.

FRET experimentFigure 1: FRET experiment demonstrating deformations of spacer DNA during promoter melting by RNA polymerase.

2. Development of novel sensors for biomolecule detection and imaging.

Our main interest in sensor research is to develop robust highly specific and sensitive molecular sensors that could be utilized in research, medical diagnosis and pathogen detection. Our sensors utilize a simple biophysical phenomenon (target-induced oligonucleotide-oligonucleotide association) to transduce the presence of the target molecule into a measurable signal. The focus of our current research is to develop highly multiplexed microarray-style assays for antibody detection that could be utilized for diagnosis, prognosis and monitoring of the progress of therapy in cancer and in autoimmune diseases.

bacterial sensor designFigure 2: Design of homogeneous sensors for detecting pathogenic bacteria (upper panel). Increased stability of the pair of antibodies bound to neighboring sites on the surface of the cell due to additional favorable free energy derived from hybridization of complementary signaling oligonucleotides (lower left panel). ) Fluorescence FRET images of 96-well microplate wells containing indicated amounts of E. coli O157:H7 cells or control cells (E. coli K12) (lower right panel).